TROP2 antibody-drug conjugate

Proximal tubular injury / ATN and proteinuria

TROP2 is expressed on tubular epithelium, and the deruxtecan (DXd) payload class already shows tubular signals with trastuzumab deruxtecan and enfortumab vedotin.

Basis: Extrapolated from the ADC class and TROP2 tissue distribution.

HER2 antibody-drug conjugate

Tubular injury and proteinuria

Scattered real-world AKI and proteinuria reports with a shared DXd topoisomerase-I payload; under-published relative to its rapidly expanding use.

Basis: Emerging case reports + ADC class effect.

DLL3×CD3 bispecific (BiTE)

CRS-driven prerenal AKI and tumor lysis

T-cell–engaging bispecifics reliably produce cytokine release syndrome with capillary leak and hemodynamic AKI, as seen across the BiTE/bispecific class.

Basis: Class effect of CD3 bispecifics (blinatumomab, teclistamab).

Menin inhibitor

Differentiation syndrome → capillary leak AKI and tumor lysis

Menin inhibitors induce leukemic differentiation; differentiation syndrome (like ATRA/IDH inhibitors) carries capillary-leak AKI and TLS risk.

Basis: Mechanistic analogy to IDH inhibitors and ATRA.

AKT inhibitor

Prerenal AKI from diarrhea; metabolic disturbance

Prominent diarrhea and hyperglycemia can drive volume depletion and prerenal injury; a direct renal lesion is not established.

Basis: Toxicity profile of the agent; no confirmed intrinsic nephrotoxicity.

HIF-2α inhibitor

Functional creatinine rise; possible true tubular effect

HIF-2α modulation alters erythropoiesis and renal physiology; observed creatinine elevations are hard to separate from co-administered TKIs.

Basis: Real-world observations, mechanism still being characterized.

KRAS G12C inhibitor

Podocyte / glomerular injury beyond the secretion artifact

The adagrasib rechallenge-positive albuminuria signal raises the possibility of a class podocyte effect; sotorasib data are still sparse.

Basis: Analogy to the adagrasib real-world signal.

Antibody-drug conjugates (broad)

Payload-specific tubular toxicity and TMA

As ADC payloads (MMAE, DM4, DXd, calicheamicin) proliferate, off-target endothelial and tubular toxicity is likely to emerge faster than dedicated renal studies.

Basis: Pattern recognition across the expanding ADC landscape.

HER2 exon20 TKI (investigational)

Benign creatinine rise via tubular secretion inhibition

Many HER2/EGFR-family TKIs inhibit tubular creatinine transporters, producing pseudo-AKI without true injury — but trial-stage renal data are absent.

Basis: Speculative extrapolation from related TKIs; no clinical renal data yet.

HIF-2α inhibitor (investigational)

Anemia-related hemodynamics; uncertain direct renal effect

By analogy to belzutifan; the renal safety profile of this trial-stage agent is genuinely unknown.

Basis: Speculative class analogy; awaiting trial data.